..Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality...

..We suggest that both IGF1R and the TGF-beta /BMP pathway could play important roles in immune function in sickle cell anemia and their polymorphisms may help identify a "bacteremia-prone" phenotype...

..Additional validation, resequencing, and functional studies to understand the biology and reveal mechanisms by which candidate genes might have their effects are the future goals of this work...

RNA editing genes associated with extreme old age in humans and with lifespan in C. elegans

Paola SebastianiDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of AmericaPLoS ONE 4:e8210. 2009

..The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered...

Genome-wide association studies and the genetic dissection of complex traits

..In this article, we will review the common approach to analysis of GWAS data and then discuss options to learn more from these data. We will use examples from our ongoing studies of sickle cell anemia and also GWAS in multigenic traits...

..Pharmacological treatment of the disease is focused on the inhibition of sickle haemoglobin polymerisation, prevention or repair of red cell dehydration and interruption of the interaction of sickle cells with the endothelium...

..Our results may provide insight into the pathogenesis of osteonecrosis in sickle cell disease, help identify individuals who are at high risk for osteonecrosis, and thus allow earlier and more effective therapeutic intervention...

..This is the second known deletion that removes the 3'-end but preserves the integrity of the 5'-end of the beta-globin gene. Furthermore, the identification of the deletion allows proper genetic counseling for affected families...

BCL11A is a major HbF quantitative trait locus in three different populations with beta-hemoglobinopathies

..This finding supports the notion that oxidative stress modulates the pathogenesis of PH of SCA and suggests that this and other post-translational modifications may be important biomarkers of disease...

A T-to-G transversion at nucleotide -567 upstream of HBG2 in a GATA-1 binding motif is associated with elevated hemoglobin F

..The T-to-G mutation in this motif disrupts GATA-1 binding and the associated repressor complex, abolishing its silencing effect and resulting in the up-regulation of gamma-globin gene expression in adults...

Effects of family history and apolipoprotein E epsilon4 status on cognitive decline in the absence of Alzheimer dementia: the Cache County Study

..Resistance vessels have preserved response to exogenous NO donors but have diminished contribution of NO to endothelium-dependent vasodilation. Conduit vessels demonstrate impaired vasodilation to endogenous and exogenous NO...

..These studies underscore the importance to correlate clinical course with laboratory diagnosis and to make DNA-based diagnostics more widely available for patients with unusual or complicated hemoglobin disorders...

..05) and a significant increase in Hsp70 levels in SCD at baseline compared with normal controls (P <0.05). Taken together, these results indicate that circulating serum Hsp70 might be a marker for VOC in SCD...

A network model to predict the risk of death in sickle cell disease

Paola SebastianiBoston University School of Public Health, MA 02118, USABlood 110:2727-35. 2007

..The severity score could serve as an estimate of overall disease severity in genotype-phenotype association studies, and the model provides an additional method to study the complex pathophysiology of sickle cell disease...

..Patients with Hb SE disease should be followed and managed in a similar fashion as those with Hb S/beta(+)-thalassemia, and treated appropriately when they develop sickling-related symptoms and complications...

N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease

..Decreased erythrocyte glutathione and glutamine levels contribute to alterations in the erythrocyte redox environment, which may compromise erythrocyte integrity, contribute to hemolysis, and play a role in the pathogenesis of PH of SCD...

James G TaylorPulmonary and Vascular Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, United States of AmericaPLoS ONE 3:e2095. 2008

..We have previously reported that intense hemolysis is associated with increased risk of vascular complications in a small cohort of adults with sickle cell disease. These observations have not been validated in other populations...

Pneumococcus and sickle cell disease: the beginning of the end?

Martin H SteinbergClin Infect Dis 44:1434-5. 2007

Effectiveness of a dedicated day hospital for management of acute sickle cell pain

Adeboye H AdewoyeHaematologica 92:854-5. 2007

..1 We report on the benefit of treating acute pain in SCD in a day hospital (DH)...